Immunoinformatic approach for multi-epitope vaccine design against Staphylococcus aureus based on hemolysin proteins.

Staphylococcus aureus is a common bacterium that causes a variety of infections in humans. This microorganism produces several virulence factors, including hemolysins, which contribute to its disease-causing ability. The treatment of S. aureus infections typically involves the use of antibiotics. However, the emergence of antibiotic-resistant strains has become a major concern. Therefore, vaccination against S. aureus has gained attention as an alternative approach. Vaccination has the advantage of stimulating the immune system to produce specific antibodies that can neutralize bacteria and prevent infection. However, developing an effective vaccine against S. aureus has proven to be challenging. This study aimed to use in silico methods to design a multi-epitope vaccine against S. aureus infection based on hemolysin proteins. The designed vaccine contained four B-cell epitopes, four CTL epitopes, and four HTL epitopes, as well as the ribosomal protein L7/L12 and pan-HLA DR-binding epitope, included as adjuvants. Furthermore, the vaccine was non-allergenic and non-toxic with the potential to stimulate the TLR2-, TLR-4, and TLR-6 receptors. The predicted vaccine exhibited a high degree of antigenicity and stability, suggesting potential for further development as a viable vaccine candidate. The population coverage of the vaccine was 94.4 %, indicating potential widespread protection against S. aureus. Overall, these findings provide valuable insights into the design of an effective multi-epitope vaccine against S. aureus infection and pave the way for future experimental validations.

Safety and effectiveness of interference RNA (RNAi) based therapeutics in cardiac failure: A systematic review.

BACKGROUND: Heart failure is a major worldwide health concern and leading cause of mortality. RNAi interventions hold promise for patients resistant to conventional drugs due to their off-target effects and lack of specificity. OBJECTIVES: To examine the safety and effectiveness of RNAi therapeutics in treating heart failure. METHODS: The PubMed, Embase, Scopus and Cochrane databases were searched using appropriate keyword from inception until December 31, 2023. A total of 14 studies fulfilling predefined selection criteria were included for qualitative synthesis. RESULTS: We found that in patients with cardiac amyloidosis, patisiran and revusiran showed considerable improvements in cardiac output and left ventricular wall thickness. In animal studies, Nox2-siRNA showed effectiveness in regaining heart function. Furthermore, cardiomyocyte count and left ventricular function were improved by DUSP5 siRNA + T3 therapy and meg3 inhibition after myocardial infarction (MI). RNAi showed minimal adverse effects like peripheral neuropathy, hepatotoxicity, urinary tract infection, vaginal infection, diarrhea, abdominal pain arrhythmias, conduction disorders, and cardiotoxicity (LV wall thinning, heart failure) and improved cardiac biomarkers. CONCLUSION: RNAi therapeutics are novel treatment option for improving cardiac function because their high target specificity, ability to target genes that conventional drugs struggle to reach and potential for long-lasting effects. Further research on optimizing delivery methods, improving target specificity, evaluating long-term safety profiles and cost-effectiveness to fully realize their potential.

Assessment of lifestyle changes in combating the COVID-19 pandemic among people of Karachi, Pakistan.

Aim: COVID-19 arose as a pandemic that wreaked havoc all over the world. Study determines lifestyle changes adopted by people of Karachi in response to COVID-19 pandemic. Methods: This was the cross-sectional study and carried out at public sector hospital and 218 participants were selected through random sampling method. Results: Lifestyle changes a statistically significant difference in nutrition (p = 0.000), physical activity (p = 0.000), workout (p = 0.000), smoking (p = 0.000), sleep hours (p = 0.000), and supplements (p = 0.000) before and during lockdown. Face masks were utilized by 38% of individuals, gloves by 19%, and social isolation was observed by 26%. 11% of participants did not follow any protocols. Conclusion: Study found significant differences in lifestyle habits such as diet, sleep, smoking and physical activity.

COVID-19 pandemic affect every day life of all people. This study results fond that there are different domain of quality life were affected. Nutrition, physical activity and smoking were associated with poor quality of life and these changes affect the mental and physical health of community people. There is need to social and medical support for people affected by COVID-19 pandemic.

Nutraceutical activities of Trigonella foenum-graecum and Nigella sativa seeds in the management of diabetes-induced in albino rats.

Diabetes causes elevated blood sugar levels, and it has been categorized as one of the most frequent causes of death worldwide. This work aimed to analyze and compare the nutraceutical and therapeutic efficacy of fenugreek seeds (FSs) (Trigonella foenum-graecum) and black cumin seeds (BCSs) (Nigella sativa) against streptozotocin-induced diabetes mellitus in albino rats. FS and BCSs were evaluated for proximate analysis, phytochemicals, and antioxidant activities. Male albino rats were used to evaluate the in vivo antidiabetic activities of these medicinal plants for 42 days. Blood samples were drawn at regular intervals of 1 week to analyze blood glucose, plasma insulin, and cholesterol levels and to determine the homeostatic model assessment of insulin resistance (HOMA IR) index. At the end of the trial, pancreas tissue was also collected for histological examination. Results of the proximate analysis showed the significant presence of moisture, ash, fat, protein, and fiber. Antioxidant parameters like 2,2-diphenyl-1-picrylhydrazyl, total phenolic content, and total flavonoid content were found to be significant. There was a significant (p < 0.05) decrease in blood glucose level, serum cholesterol level, and insulin resistance in treatment groups T3-T5. Insulin and body weight results of treatment groups were significant (p < 0.05) compared to streptozotocin-intoxicated animals. Histological examination revealed the nutraceutical impact of selected herbal plants due to enhancing impact on the size and the number of ß-cells in the pancreas. Findings of current research work explore the antidiabetic capacity of selected nutraceutical and medicinal plants.

Primary Hyperparathyroidism With Brown Tumor of the Mandible Misdiagnosed as a Giant Cell Tumor: A Case Report.

In this case study, we present an incidentally discovered giant cell granuloma, which, upon detailed investigation, led to an unexpected diagnosis. A 36-year-old woman exhibited a bone lesion in the right retromolar trigone area, initially suspected of being malignant. However, histopathological examination revealed a giant cell tumor of bone. Further biochemical profiling, including serum calcium, phosphorus, and parathyroid hormone (PTH) levels, showed elevated PTH and hypercalcemia, prompting consideration of primary hyperparathyroidism and the diagnosis of a brown tumor due to this condition. This case underscores the importance of considering brown tumors associated with primary hyperparathyroidism as a potential differential diagnosis in patients with lytic bone lesions.

Screen Time And Its Relationship With Attention Deficit Hyperactivity Disorder Among Children Attending A Tertiary Care Hospital.

Objective: To estimate the frequency of attention deficit hyperactivity disorder and its relationship with screen time and sociodemographic characteristics among children. METHODS: The cross-sectionalstudy was conducted at the National Institute of Child Health, Karachi, in June-July 2022, and comprised children of either gender aged 5-10 years visiting the paediatric outpatient department. Screen time was measured using a pretested questionnaire, while attention deficit hyperactivity disorder was measured using ADHD rating scale IV. The relationship of sociodemographic characteristics and screen time with the disorder was explored through multiple linear regression analysis. Data was analysed using SPSS 20. RESULTS: Of the 247 participants, 126(51%) were boys and 121(49%) were girls. The overall mean age was 7.84±1.87 years. There were 149(60.3%) children at the primary level of education, while 76(30.8%) had no formal education. There were 139(56.3%) children having screen time >2 hours/day with a mean of 3.36±3.14 hours. There were 15(6.1%) children with attention deficit hyperactivity disorderscore >26 with a mean of 11.58±9.27. Boys were more frequently affected by attention deficit hyperactivity disorder compared to girls (p=0.026), and there was a significant positive correlation between screen time and attention deficit hyperactivity disorder (p<0.001). Conclusion: The majority of children were found to be spending more than the recommended time on screen. Male gender and screen time were associated with attention deficit hyperactivity disorder.

The Release Behavior of Anthraquinones Encapsulated into Casein Micelles during In Vitro Digestion.

The degradation of anthraquinones extracted from aloe vera plants can be prevented by encapsulating them in casein micelles (CMs). The oral, gastric, and intestinal digestion behavior of spray-dried microcapsules of casein micelles loaded with aloe vera-extracted anthraquinone powder (CMAQP), freeze-dried powder (CMFDP), and whole-leaf aloe vera gel (CMWLAG) obtained through ultrasonication was investigated. The results found that CMAQP and CMFDP dissolved slowly and coagulated into large curds during gastric digestion, improving the retention of anthraquinones in the digestive tract. In contrast, CMWLAG structure was destroyed and increased amounts of anthraquinones were released during oral and gastric digestion phases, indicating increased amounts of surface anthraquinones instead of the encapsulation of anthraquinones in the interior of CMs. The strong hydrophobic interactions protected anthraquinones within the core of CM for CMAQP and delayed diffusion. However, during SIF digestion, both CMAQP and CMFDP released significant amounts of anthraquinones, although CMAQP showed a much more controlled release for both aloin and aloe-emodin over SIF digestion time. The release behavior of anthraquinones from CM microcapsules was a function of the type of anthraquinone that was used to encapsulate. The present study provides insight into the release behavior of loaded bioactive compounds using food-grade CMs as the wall material during in vitro digestion and highlights the importance of the type of bioactive component form that will be encapsulated.

Invasive Fungal Rhinosinusitis: Clinical and Surgical Factors Affecting Its Prognosis and Disease-Specific Morality.

PURPOSE: The purpose of this study is to discover factors that determine mortality in patients with invasive fungal rhinosinusitis. METHODS: This retrospective study included 17 patients diagnosed with invasive fungal rhinosinusitis and who had undergone treatment in our department, including both surgical and medical management between January 2020 and October 2020. There were four male patients and 13 female patients whose mean age was 46 ± 15.67 years, ranging from 20 to 70 years. All the patients were immune-compromised because of diabetes mellitus. We studied the factors affecting the mortality of patients affected with this disease; it included the extent of disease (paranasal sinus, palatal, orbital, or intracranial involvement), serum glucose level (SGL), and C-reactive protein (CRP) levels. RESULTS: Only one patient had paranasal sinus involvement alone, but the patient became disease-free after treatment. The disease-specific mortality rate was two (33.3%) of six patients with palatal involvement and four (50%) of eight patients with intracranial involvement where four patients did not have disease control at the time of discharge and did not follow up. The death rate in orbital involvement was 20% (three of 15 patients) and five patients with intra-orbital involvement left the hospital against medical advice. The analysis of data demonstrated that only intracranial (p = 0.01) involvement in addition to the nasal cavity and paranasal sinus involvement had a statistically significant effect on survival rate unlike intra-orbital (p = 0.510) and palatal involvement (p = 0.171). CONCLUSION: Early endoscopic nasal inspection, diagnosis, and treatment are critical for disease-specific mortality in invasive fungal rhinosinusitis since orbital or cerebral involvement is linked to a poor prognosis. Patients who come with uncontrolled diabetes and ophthalmological and palatal involvement with positive findings on nasal examination should necessitate urgent histopathological and radiological workup.

Antibiotic Utilization Patterns for Different Wound Types among Surgical Patients: Findings and Implications.

Antimicrobial prophylaxis is effective in reducing the rate of surgical site infections (SSIs) post-operatively. However, there are concerns with the extent of prophylaxis post-operatively, especially in low- and middle-income countries (LMICs). This increases antimicrobial resistance (AMR), which is a key issue in Pakistan. Consequently, we conducted an observational cross-sectional study on 583 patients undergoing surgery at a leading teaching hospital in Pakistan with respect to the choice, time and duration of antimicrobials to prevent SSIs. The identified variables included post-operative prophylactic antimicrobials given to all patients for all surgical procedures. In addition, cephalosporins were frequently used for all surgical procedures, and among these, the use of third-generation cephalosporins was common. The duration of post-operative prophylaxis was 3-4 days, appreciably longer than the suggestions of the guidelines, with most patients prescribed antimicrobials until discharge. The inappropriate choice of antimicrobials combined with prolonged post-operative antibiotic administration need to be addressed. This includes appropriate interventions, such as antimicrobial stewardship programs, which have been successful in other LMICs to improve antibiotic utilization associated with SSIs and to reduce AMR.

An Unusual Presentation of type-IV Second Branchial Cyst: A Case Report.

Second branchial cleft cysts are a cystic dilatation of the remnant of the second branchial cleft that account for 95-percent of all branchial cleft malformations, along with second branchial fistulae and sinuses. Among them, the type-IV second branchial cyst is present against the pharyngeal wall in the parapharyngeal space and is rarest of all. Herein we report a rare presentation of type-IV second branchial cyst where MRI played a critical role for accurate preoperative diagnosis. The transcervical approach is a safe and effective technique for proper exposure and hence total surgical excision in such cases.

Chimeric vaccine designs against Acinetobacter baumannii using pan genome and reverse vaccinology approaches.

Acinetobacter baumannii (A. baumannii), an opportunistic, gram-negative pathogen, has evoked the interest of the medical community throughout the world because of its ability to cause nosocomial infections, majorly infecting those in intensive care units. It has also drawn the attention of researchers due to its evolving immune evasion strategies and increased drug resistance. The emergence of multi-drug-resistant-strains has urged the need to explore novel therapeutic options as an alternative to antibiotics. Due to the upsurge in antibiotic resistance mechanisms exhibited by A. baumannii, the current therapeutic strategies are rendered less effective. The aim of this study is to explore novel therapeutic alternatives against A. baumannii to control the ailed infection. In this study, a computational framework is employed involving, pan genomics, subtractive proteomics and reverse vaccinology strategies to identify core promiscuous vaccine candidates. Two chimeric vaccine constructs having B-cell derived T-cell epitopes from prioritized vaccine candidates; APN, AdeK and AdeI have been designed and checked for their possible interactions with host BCR, TLRs and HLA Class I and II Superfamily alleles. These vaccine candidates can be experimentally validated and thus contribute to vaccine development against A. baumannii infections.

Designing Multi-Epitope Vaccines to Combat Emerging Coronavirus Disease 2019 (COVID-19) by Employing Immuno-Informatics Approach.

A recent pandemic caused by a single-stranded RNA virus, COVID-19, initially discovered in China, is now spreading globally. This poses a serious threat that needs to be addressed immediately. Genome analysis of SARS-CoV-2 has revealed its close relation to SARS-coronavirus along with few changes in its spike protein. The spike protein aids in receptor binding and viral entry within the host and therefore represents a potential target for vaccine and therapeutic development. In the current study, the spike protein of SARS-CoV-2 was explored for potential immunogenic epitopes to design multi-epitope vaccine constructs. The S1 and S2 domains of spike proteins were analyzed, and two vaccine constructs were prioritized with T-cell and B-cell epitopes. We adapted a comprehensive predictive framework to provide novel insights into immunogenic epitopes of spike proteins, which can further be evaluated as potential vaccine candidates against COVID-19. Prioritized epitopes were then modeled using linkers and adjuvants, and respective 3D models were constructed to evaluate their physiochemical properties and their possible interactions with ACE2, HLA Superfamily alleles, TLR2, and TLR4.

Formal model of the interplay between TGFß1 and MMP-9 and their dynamics in hepatocellular carcinoma.

Transforming growth factor beta1 (TGFß1) and matrix metalloproteinase-9 (MMP-9) have been associated with migration and invasion in hepatocellular carcinoma (HCC). Recent studies have suggested a positive feedback loop between TGFß1 and MMP-9 mediated by the PI3K signaling pathway that confers acquired invasion and metastasis in HCC via induction of the epithelial-mesenchymal transition (EMT), which grows into invasive carcinoma. But the potential molecular mechanism of this loop on HCC has not been clarified yet. Therefore, this study is designed to explore the association between the two entities and their key determinants such as NFκB, TIMP-1, and hepatic stellate cells (HSCs). Hence, a qualitative modeling framework is implemented that predict the role of biological regulatory network (BRN) during recovery and HCC metastasis. Qualitative modeling predicts discrete trajectories, stable states, and cycles that highlight the paths leading to disease recovery and homeostasis, respectively. The deadlock stable state (1, 1, 1, 1, 1) predicts high expression of all the entities in the BRN, resulting in the progression of HCC. The qualitative model predicts 30 cycles representing significant paths leading to recovery and homeostasis and amongst these the most significant discrete cycle was selected based on the highest betweenness centralities of the discrete states. We further verified our model with network modeling and simulation analysis based on petri net modeling approach. The BRN dynamics were analyzed over time. The results implied that over the course of disease condition or homeostasis, the biological entities are activated in a variable manner. Taken together, our findings suggest that the TGFß1 and the MMP-9 feedback loop is critical in tumor progression, as it may aid in the development of treatment strategies that are designed to target both TGFß and MMP-9.

Reverse Vaccinology Approach to Potential Vaccine Candidates Against Acinetobacter baumannii.

Acinetobacter baumannii is a rapidly evolving pathogen that largely inhabits intensive care units (ICU). This opportunistic, gram-negative organism has shown noteworthy taxonomic variations during the past three decades. A. baumannii functions as a catalase-positive, oxidase-negative obligate, aerobic, nonmotile, highly infectious, and multidrug-resistant bacterium. Therefore, the infection caused by this bacterium tends to have a fairly higher incidence rate in immune-compromised individuals ranging from 26.5% to 91%, as it colonizes in skin tissues and secretions of the respiratory tract. Recently, it has been globally labeled as a "red alert" pathogen, setting alarms throughout the medical community, arising mainly due to its widespread antibiotic resistance continuum. There is a dire need for alternative therapeutic intervention to combat A. baumannii-associated infections and the growing resistance. This chapter focuses upon the reverse vaccinology-based steps and strategies to identify novel potential vaccine candidates against this emerging pathogen.

Novel Echocardiographic Parameters in Patients With Aortic Stenosis and Preserved Left Ventricular Systolic Function Undergoing Surgical Aortic Valve Replacement.

We sought to study the incremental prognostic impact of baseline valvuloarterial impedance (Zva) and left ventricular global longitudinal strain (LV-GLS) in patients with severe aortic stenosis and preserved left ventricular ejection fraction (LVEF) treated with surgical aortic valve replacement (AVR). We included 961 consecutive patients (68 ± 13 years; 63% men) with severe aortic stenosis (indexed aortic valve area <0.6 cm2) and LVEF >50% who underwent surgical AVR at our institution between January 2007 and December 2008. The analysis is based on derivation (n = 637) and validation (n = 324) subgroups. Society of Thoracic Surgeons (STS) score was calculated. Zva (systolic arterial pressure + mean aortic valve gradient)/left ventricular stroke volume index and LV-GLS (measured offline using Velocity Vector Imaging; Siemens Medical Solutions, Mountain View, California) were calculated. The primary outcome was death. Median Zva and LV-GLS were 4.5 mm Hg × ml-1 × m2 and -14.5%, respectively. AVR was performed at a median of 34 days from initial evaluation (isolated AVR in 46%, bioprosthetic AVR in 93%). At 7.5 ± 3 years, 320 patients died (33%; 30 days/in-hospital death in 0.5%). In the derivation subgroup, on multivariate Cox survival analysis, higher STS score (hazard ratio [HR] 1.06), higher Zva (HR 1.13), and worse LV-GLS (HR 1.07) were independently associated with long-term survival (all p <0.01). When Zva and LV-GLS were sequentially added to STS score, the c-statistic improved from 0.63 [0.55 to 0.77] to 0.70 [0.60 to 0.81] and 0.78 [0.69 to 0.83], respectively, all p <0.001). Findings were confirmed in the validation subgroup. In conclusion, in patients with severe aortic stenosis and preserved LVEF treated with surgical AVR, baseline Zva and LV-GLS provide improved risk stratification with synergistic prognostic value.

Upper gastrointestinal endoscopy: expected post-procedural findings and adverse events.

Complications related to endoscopy are commonly encountered in the emergency department (ED) due to an increased use of outpatient diagnostic and therapeutic upper gastrointestinal endoscopic procedures. A majority of these procedures are performed on an outpatient basis, and patients with post-procedural symptoms may return to the ED. Since these patients often undergo computed tomography (CT) for diagnosis of post-procedure complications, the emergency radiologist should be familiar with the spectrum of expected post-procedural findings, as well as common and rare complications. We present a pictorial review of post-endoscopy complications and review imaging protocols in different clinical scenarios.

Assessment of blood donation intention among medical students in Pakistan--An application of theory of planned behavior.

OBJECTIVE: Theory of Planned Behavior proposes a model which can measure how human actions are guided. It has been successfully utilized in the context of blood donation. We employed a decision-making framework to determine the intention of blood donation among medical students who have never donated blood before the study. METHODS: Survey responses were collected from 391 medical students from four various universities on a defined questionnaire. The tool composed of 20 questions that were formulated to explain donation intention based on theory of planned behavior. The construct included questions related to attitude, subjective norm and perceived behavior control, descriptive norm, moral norm, anticipated regret, donation anxiety and religious norm. Pearson's correlational relationships were measured between independent and dependent variables of intention to donate blood. ANOVA was applied to observe the model fit; a value of 0.000 was considered statistically significant. A multiple regression analysis was conducted to explore the relative importance of the main independent variables in the prediction of intention. Multi-collinearity was also evaluated to determine that various independent variables determine the intention. The reliability of measures composed of two items was assessed using inter-item correlations. RESULTS: Three hundred and ninety-one medical students (M:F; 1:2.2) with mean age of 21.96 years ± 1.95 participated in this study. Mean item score was 3.8 ± 0.83. Multiple regression analysis suggested that perceived behavioral control, anticipated regret and attitude were the most influential factors in determining intention of blood donation. Donation anxiety was least correlated and in fact bore a negative correlation with intention. ANOVA computed an F value of 199.082 with a p-value of 0.000 indicating fitness of model. The value of R square and adjusted R square was 0.811 and 0.807 respectively indicating strong correlation between various independent and dependent variables. CONCLUSIONS: Medical students as novice blood donors showed a positive attitude toward blood donation. Theory of planned behavior can be successfully utilized in determining the antecedents toward blood donation behavior.

Tetralogy of Fallot with absent pulmonary valve syndrome; appropriate surgical strategies.

OBJECTIVE: To evaluate patients presenting with Tetralogy of Fallot with absent pulmonary valve syndrome to a tertiary care hospital and their surgical management. METHODS: The retrospective study was conducted at Congenital Cardiac Services, Aga Khan University Hospital, Karachi, Pakistan, and comprised data of Tetralogy of Fallot patients between April 2007 and June 2012. Data was analysed together with follow-up echocardiography. Variables assessed included demographics, imaging, operative technique, complications, post-operative recovery and follow-up echocardiography. SPSS 17 was used for statistical analysis. RESULTS: Of the 204 patients, 6 (3%) had undergone surgical correction for Tetralogy of Fallot with absent pulmonary valve syndrome. All 6(100%) patients underwent complete repair. Median age for surgery was 8.5 years (range: 0.5-29 years). Of the different surgical strategies used, Contegra and Bioprosthetic valve placement had satisfactory outcome with minimal gradient at Right Ventricular Outflow Tract, good ventricular function and mild valvular regurgitation. One (16.6%) patient with Trans Annular Patch developed post-operative Right Ventricle Outflow Tract gradient of 80mmHg with moderate pulmonary regurgitation. One (16.6%) patient with monocusp valve developed free pulmonary regurgitation at 6 months. The other 4(66.6%) patients are currently free from any complications or re-intervention. CONCLUSIONS: Early surgery is preferred in symptomatic patients. The repair depends upon achieving integrity of pulmonary circulation which is best achieved by using right ventricle to pulmonary artery conduit or inserting a pulmonary valve.